Let 1,000 genomes bloom

Hoping to get a grip on human genetic diversity, a multinational consortium is …

Although the completion of the human genome was rightly portrayed as a triumph, it left a number of questions unanswered. Perhaps the most significant issue was how well the final product represented a "typical" human genome. What researchers care about most—mutations and variations that predispose their carriers to genetic diseases—are differences from that average sequence, and are often identified due to their linkage to yet other variations. It has also become clear that the average human may have additional copies of some regions of the genome, which may influence the expression of the genes in that area. An international consortium of genomics researchers has now announced the next step in coming to grips with this diversity: the 1,000 Genomes project.

The basic idea is to go a step beyond the existing human HapMap, which is a catalog of the common variations present in the human genome, and sequence enough individuals to identify the uncommon variations. The goal is to identify all base differences that occur in as little as one percent of the population, with even finer resolution available in gene-rich regions. Unlike the original HapMap, the new data will also be generated with copy number variations in mind, so it will provide a greater sense of the structural diversity of the human population.

The effort will face two challenges. The first is in its equipment. Several methods that make genome sequencing cheaper and faster have reached the market in the past few years, but no one has had the ability to compare and evaluate their relative performance and accuracy. The consortium behind this effort, which includes the genome centers at The Sanger Institute, Beijing Genomics Institute, Broad Institute, Baylor College of Medicine, and Washington University, have nearly 75 of the next-generation machines among them. Pilot projects will evaluate the relative effectiveness of these technologies for the task.

The second aspect that needs to be tested is the method. Is it better to skim the sequence of many individuals, or take a detailed look at the genomes of fewer of them? There is no way of knowing in advance, so the project will involve trying both on a small scale, and possibly continue doing so if the two approaches work in a complementary manner. Details of these and other decisions are available in a summary (PDF) of the meeting that helped get the project off the ground.

Ultimately, the project is likely to make the lives of medical researchers much easier, as they won't have to spend time developing their own genetic markers when chasing down rare traits. But it will also give all of us a clearer picture of just how much variation has developed within the human population in the 100,000 years or so that we've been expanding away from our African origin.